Some types of implantable medical devices, such as cardiac pacemakers or implantable cardioverter defibrillators, provide therapeutic electrical stimulation to a heart of a patient via electrodes of one or more implantable leads. The therapeutic electrical stimulation may be delivered to the heart in the form of pulses or shocks for pacing, cardioversion or defibrillation. In some cases, an implantable medical device may sense intrinsic depolarizations of the heart, and control the delivery of therapeutic stimulation to the heart based on the sensing.
Cardiac resynchronization therapy (CRT) is one type of therapy delivered by an implantable medical device. Cardiac resynchronization therapy may help enhance cardiac output by resynchronizing the electromechanical activity of the ventricles of the heart. Ventricular desynchrony may occur in patients that suffer from heart failure (HF).
CRT is one of the most successful heart failure (HF) therapies to emerge in the last 25 years and is applicable to 25-30% of patients with symptomatic HF, especially those with abnormal impulse conduction through the ventricles, such as left bundle branch block (LBBB). Since initial approval of the therapy over 10 years ago, there have been hundreds of thousands of implants worldwide. Although the effects of CRT on the population level are impressive, benefits at the individual level vary considerably. Depending on the definition, the response to CRT is positive in 50-70% of patients, leaving 30-50% without significant effect. Such lack of response is especially not desirable, since CRT requires the virtually irreversible implantation of a costly device and pacing electrodes during an invasive procedure.
Effectiveness of CRT can be improved by optimal programming of the device, especially with regard to the time delay (A-V delay) between activation (e.g., intrinsic or in response to electrical stimulation) of the right atrium (RA) and electrical stimulation of the ventricles and the time delay (V-V interval) between activation of the right ventricle (RV) and stimulation of the left ventricle (LV). Such CRT optimization increases acute hemodynamic benefits of CRT by 20-30% and improves short-term clinical response. In half of CRT clinical non-responders it is believed that symptoms could be improved by careful A-V interval and V-V interval optimization. However, in regular clinical practice, “out-of-the-box” default settings are often used for these intervals. Furthermore, echocardiographic techniques can be used to optimize A-V and V-V intervals, but such optimization procedures are relatively complicated procedures and the echocardiographic measurements are notoriously inaccurate. A further serious limitation of echocardiographic optimization is that it is performed in the recumbent position in full rest, while optimization is likely more required under more conditions of higher physical activity.
Evidence has been collected in animal experiments and CRT patients that the QRS complex in the vectorcardiogram (VCG), measured at the body surface, provides an accurate description of the degree of resynchronization during the various AV- and VV-intervals. The results of this study are presented in “Vectorcardiography as a tool for easy optimization of cardiac resynchronization in canine LBBB hearts”; Van Deursen, et al, Circ. Arrhythm. Electrophysiol, 2012; 5:544-522, incorporated herein by reference in its entirety. This study also showed that accuracy of QRS vector determination is considerably higher than that of hemodynamic measurements.
Subsequently, in a group of 11 patients, it was observed that the best hemodynamic response (“VTILVOT”) and the most physiological contraction pattern (minimal value of SPS+SRS) occur at A-V and V-V intervals where the three-dimensional area of the QRS-complex on the VCG loop (QRSVarea) is minimal. This observation is described, for example, U.S. Pat. No. 9,248,294 B2 to Prinzen et al., issued Feb. 2, 2016, the disclosure of which is incorporated by reference in its entirety herein. This minimal QRS-area, which can be determined using surface ECG measurements, provides an easy and accurate index for initial programming of optimal A-V and V-V intervals. FIG. 1 of U.S. Pat. No. 9,248,294 B2 illustrated the use of a surface VCG for optimization of CRT, showing data from a representative CRT patient. The A-V delay at which QRSV area was minimal coincided with the A-V delay where a minimal value was found for the sum of septal systolic pre-stretch (SPS) and rebound stretch (SRS; indicating the least abnormal septal contraction) as well as the highest value of VTILVOT (˜stroke volume). In 11 patients, the difference between actual maximal increase in VTILVOT relative to LBBB and VCG-predicted increase was small (−0.4%; IR −1.6 to 0% and −0.5%; IR −1.3 to −0.2% respectively). Surface VCGs thus provide a useful tool in conjunction with both initial implant and later follow-up visits for adjustment of stimulation parameters.
In this prior study, the inventors also found that the measured surface QRS vector amplitude also could be used to optimize A-V and V-V delays. In this case, the combination of A-V and V-V intervals that produced a surface QRS vector amplitude halfway between that seen during LV pacing at short A-V intervals and that seen during un-paced LBBB rhythm corresponded to minimal QRSV area and to optimal hemodynamic performance.